Elucidating the molecular regulation of viral gene expression may lead to new modalities of antiviral therapy. By genetic and biochemical analyses, our laboratory has demonstrated the existence of a novel genetic element (HRL) within the HBV genome that is important for efficient expression of viral gene products. This genetic element is cis-acting at the posttranscriptional level, and that its function is exerted at the level of RNA processing as part of transcribed sequences. Similar to the function of Rev-RRE interaction of HIV-1, this element appears to inhibit the splicing process and facilitate the transport and utilization of HBV transcripts. This HRL element may also play an important role in the pathogenesis and host response of HBV infection. We are conducting additional experiments to define the precise sequence requirement, to elucidate the molecular and biochemical mechanisms, and to study the regulatory effects of cytokines on the function of this element. Understanding the biological significance of this HRL element in viral life cycle will further our understanding of the pathogenesis and clinical expression of HBV infection.